In other species: dog , ass (donkey) , Arabian camel , llama , taurine cattle , goat , sheep , rabbit , golden hamster , domestic guinea pig , domestic yak , alpaca

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 190330 (trait) , 165190 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0008593: trichomegaly

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: no

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Long hair = angora

Species-specific symbol: l

Inheritance: Long hair is autosomal recessive, short hair is dominant.

Mapping: Kehler et al. (2007) mapped the "long-haired" phenotype to an estimated 10-Mb region on cat chromosome B1 containing the Fibroblast Growth Factor 5 (FGF5) gene, a candidate gene implicated in regulating hair follicle growth cycle in other species.

Molecular basis: Drögemüller et al. (2007) and Kehler et al (2007) proposed several likely causal variants as well as variants associated with long hair in cats and the findings are summarised by Sheffer et al. (2021): “Mutation 1 (M1), is an insertion of a thymine base (c.ins356T) originally found in the Ragdoll breed; Mutation 2 (M2), is a cytosine to thymine conversion (c.406C > T) originally found in the Norwegian Forest Cat breed; Mutation 3 (M3), is a deletion of a thymine base (c.del474T) originally found in Ragdoll and Maine Coon breeds; and Mutation 4 (M4), is an adenine to cytosine conversion (c.475A > C) found in most longhair cat breeds (Drögemüller et al 2007; Kehler et al 2007). All four variants can be found in a homozygous state or a compound heterozygous state involving multiple variants (Kehler et al 2007). Two additional variants in FGF5 [c.194C>A, p.(P65H) and c.182T>A, p.(V61D); removed from likely causal variant table below on 20/10/2021] were identified by Drögemüller et al. (2007) as potentially causative for the longhair phenotype. However, Kehler et al. (2007) found multiple shorthaired cats homozygous for these two mutations and excluded these variants as causative. … Both groups found the M4 variant, but it is worth mentioning that Drögemüller et al. (2007) found a single shorthaired crossbred cat that was homozygous for M4. This cat was probably incorrectly phenotyped (Leeb, personal communication). In contrast, Kehler et al. (2007) found that M4 was the most common mutation among longhaired cats and was not found in a homozygous state in any shorthaired cats in their large study.” Sheffer et al. (2021): “Sequencing of FGF5 in samples from two … Maine Coons that had only one of the four known FGF5 variants, with additional screening in 144 Maine Coon cats and confirmation in relatives, led to the identification of a fifth, novel variant, Mutation 5, (M5) associated with longhair in the Maine Coon.”

Prevalence: Kehler et al. (2007) report FGF5 allele frequencies for variants M1-M4 among 116 cats from 26 registered breeds. Variants M1-M3 are reported each in a single breed (see variant table below). Variant M4 is reported across multiple long hair breeds (Angora, Balinese, Birman, Himalayan, Maine Coon, Norwegian Forest Cat, Persian, Ragdoll, Siberian, Somali, Turkish Angora, Turkish Van, Manx, Scottish Fold) and reported to be present in heterozygous state in some short-haired breeds (British Shorthair, Devon Rex). Variant M5 is reported as an additional variant in Main Coon cats by Sheffer et al. (2021).

Associated gene: